Cell type-specific signal transducers provide potential targets for either interrupting or enhancing function of specific cell subsets. CD22 is a B lineage specific membrane protein that mediates cell-cell interactions via a sialic acid dependent mechanism; within its intracellular domain it contains several motifs that can activate signaling pathways. The tyrosine kinases Lyn and Syk the lipid kinase PI-3 kinase the serine/threonine kinases Erk1 and Erk2 and the phosphastase SHP1 all associate with CD22 either prior to or following CD22 cross linking. Syk specifically phosphorylates tyrosine residues in the intracellular portion of CD22 allowing other proteins to associate with CD22. CD22 cross linking leads to activation of the mitogen activated Protein (MAP) and stress activated protein (SAP) kinase pathways resulting in activation of AP-1. The physiologic role of CD22 in B cell immune function is being addressed by gene targeting and the generation of CD22 transgenic mice. Two interesting kinases found in B cells GCK1 and GCK2, specifically activate the SAP kinase pathway. The two proteins have very similar catalytic domains, but they have significantly different carboxyl terminal regulatory domains. While both proteins activate the SAP kinase pathway, GCK1 is superior to GCK2. Both proteins require SEK1 to activate this pathway. In contrast to the SAP kinase pathway, GCK2 failed to activate the related MAP kinase pathway and, in fact, they specifically inhibit its activation indicating that their activation biases the cell toward the SAP kinase pathway. Both GCK1 and GCK2 phosphorylate proline rich substrates and they both efficiently phosphorylate myelin basic protein. We have recently shown that the betagamma subunits of heterotrimeric G proteins significantly increase the activity of GCK2. Another very potent activator of GCK2 is oncogenic Ras. Alterations of Ras are commonly found in human tumors. Over expression of a constitutively active Ras dramatically increases the catalytic activity of GCK2. Thus, GCK2 may serve to link Ras to the SAP kinase pathway and to mediate signals generated through signaling pathways that activate Ras.